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<title>23 July, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Process evaluation of an urban piped water supply infrastructure improvement programme in a cholera hotspot</strong> -
<div>
Large-scale investments in water supply infrastructure will be required to achieve Sustainable Development Goal (SDG) 6. Safely managed water services are also a central element of global strategies to prevent cholera and diarrhoeal diseases. However, evidence remains scarce on how to efficiently improve piped water services in the complex settings that bear high disease burdens and where infrastructure investments are most needed. We conducted a process evaluation of a large-scale water supply infrastructure improvement programme in the town of Uvira, an endemic cholera hotspot in South Kivu, Democratic Republic of the Congo. Considering three evaluation domains – context, implementation of the intervention, and population response –, we assessed the validity of the programme’s theory of change and its underlying assumptions. Information sources included documents related to construction works and to the programme implementation, operational and billing records from the water system operator, and household surveys, covering the period from 2014 until 2021. The programme did not achieve the expected improvements in the water supply service available to the population of Uvira during the evaluation period. Contextual challenges included major events such as extreme flooding in early 2020 and the Covid-19 pandemic. Issues related to the electricity supply and the rise of Lake Tanganyika emphasise the need for cross-sectoral approaches and consideration of climate change in the planning of water supply infrastructure. Implementation challenges underlined a need for capacity strengthening alongside infrastructure improvements. Population response elements revealed the importance of designing affordable interventions and of taking informal practices such as the sharing of household taps into account. The programme was a good example of early engagement with researchers. Pragmatic evaluation approaches combining relevant methods should be adopted for the generation of useful scientific evidence from complex programmes in order to inform and enhance the effectiveness of future infrastructure investments contributing to progress towards SDG6.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/dpnqh/" target="_blank">Process evaluation of an urban piped water supply infrastructure improvement programme in a cholera hotspot</a>
</div></li>
<li><strong>The multi-dimensional challenges of controlling respiratory virus transmission in indoor spaces: Insights from the linkage of a microscopic pedestrian simulation and SARS-CoV-2 transmission model</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
SARS-CoV-2 transmission in indoor spaces, where most infection events occur, depends on the types and duration of human interactions, among others. Understanding how these human behaviours interface with virus characteristics to drive pathogen transmission and dictate the outcomes of non-pharmaceutical interventions is important for the informed and safe use of indoor spaces. To better understand these complex interactions, we developed the Pedestrian Dynamics - Virus Spread model (PeDViS): an individual-based model that combines pedestrian behaviour models with virus spread models that incorporate direct and indirect transmission routes. We explored the relationships between virus exposure and the duration, distance, respiratory behaviour, and environment in which interactions between infected and uninfected individuals took place, and compared this to benchmark at risk interactions (1.5 metres for 15 minutes). When considering aerosol transmission, individuals adhering to distancing measures may be at risk due to build-up of airborne virus in the environment when infected individuals spend prolonged time indoors. In our restaurant case, guests seated at tables near infected individuals were at limited risk of infection but could, particularly in poorly ventilated places, experience risks that surpass that of benchmark interactions. Combining interventions that target different transmission routes can aid in accumulating impact, for instance by combining ventilation with face masks. The impact of such combined interventions depends on the relative importance of transmission routes, which is hard to disentangle and highly context dependent. This uncertainty should be considered when assessing transmission risks upon different types of human interactions in indoor spaces. We illustrated the multi-dimensionality of indoor SARS-CoV-2 transmission that emerges from the interplay of human behaviour and the spread of respiratory viruses. A modelling strategy that incorporates this in risk assessments can help inform policy makers and citizens on the safe use of indoor spaces with varying inter-human interactions.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.04.12.21255349v2" target="_blank">The multi-dimensional challenges of controlling respiratory virus transmission in indoor spaces: Insights from the linkage of a microscopic pedestrian simulation and SARS-CoV-2 transmission model</a>
</div></li>
<li><strong>How can selective processing of vaccination information be diminished? Effects of mindsets and kinds of information</strong> -
<div>
Background: Selective processing of attitude-consistent information is a substantial obstacle in convincing vaccine-skeptical people of the benefits of vaccinations. This study tests (i) which types of information are particularly prone to such selective information processing, and (ii) whether a deliberative (vs. implemental) mindset focusing on potential benefits and harms may diminish its effects. Design: 612 Mturk participants were randomized into an implemental or deliberative mindset and received a flu vaccine-skeptical narrative, a flu vaccination facts box transparently summarizing risks and benefits, and a message by the Center for Disease Prevention and Control (CDC) in favor of the flu vaccine either referring to COVID-19 or not. We tested how these variations affected the acceptance of and the willingness to share each message. Furthermore, we evaluated their impact on flu vaccination attitudes and intentions. Results: The mindset manipulation failed to diminish generally prevalent selective information processing. While vaccine-skeptics did not accept and like the CDC message referring to COVID-19 (particularly in a deliberative mindset), they generally accepted the vaccination facts box more readily compared to both CDC messages. Conclusion: While mindsets were ineffective, more general and transparent information may be more likely to reach an anti-vaccine audience.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/5k9hw/" target="_blank">How can selective processing of vaccination information be diminished? Effects of mindsets and kinds of information</a>
</div></li>
<li><strong>Predicting Depression and Anxiety Among Adults with Disabilities During the COVID-19 Pandemic</strong> -
<div>
Purpose/Objective: Emerging research has highlighted sources of magnified stress and trauma for people with disabilities during the COVID-19 pandemic, as compared to others in the general population. However, little research has examined the mental health impact of the pandemic on people with disabilities in relation to disability-related stigma, social isolation, and demographic characteristics. The present study therefore sought to identify predictors of depression and anxiety symptoms among U.S. adults with disabilities during the COVID-19 pandemic. Research Methods/Designs: Data were collected online between October and December 2020. U.S. adults with disabilities (n = 441) completed self-report measures of depression, anxiety, psychosocial processes, and a range of demographic and disability characteristics. Results: In our sample, 61.0% and 50.0% of participants met criteria for a probable diagnosis of major depressive disorder and generalized anxiety disorder, respectively. Participants also experienced significantly higher levels of disability-related stigma and social isolation compared to pre-pandemic norms. Hierarchical regression analyses identified higher social isolation, presence of chronic pain, younger age, higher disability-related stigma, and higher worries about contracting COVID-19 as significant predictors of both depression and anxiety symptoms. Conclusion/implications: This study highlights important demographic and psychosocial predictors of mental health risks for people with disabilities in the context of COVID-19. Findings further underscore the need to attend to those at elevated risk within the disability community as rehabilitation professionals, disability organizations, and policymakers work to support people with disabilities in post-pandemic recovery and create a more equitable response to ongoing and future public health crises.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/zne42/" target="_blank">Predicting Depression and Anxiety Among Adults with Disabilities During the COVID-19 Pandemic</a>
</div></li>
<li><strong>Narrative identity among people with disabilities during the COVID-19 pandemic: The interdependent self</strong> -
<div>
This study examines narrative identity among a large, diverse (American) sample of people with disabilities (PWDs) during the “second wave” of the COVID-19 pandemic (October-December, 2020). The study relied on abductive analyses, combining a purely inductive phase of inquiry followed by two rounds of investigation that filtered inductive insights through three theoretical lenses: social-ecological theory, the theory of narrative identity, and perspectives from the interdisciplinary field of disability studies. The central result was the identification of a particular configuration of self, one that was demonstrably interdependent with both immediate interpersonal contexts and with broader cultural contexts. This interdependent self was interpreted in both positive and negative ways by PWDs. These findings invite future inquiry into commonplace conceptualizations of an independent self at the center of personality research.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/6724x/" target="_blank">Narrative identity among people with disabilities during the COVID-19 pandemic: The interdependent self</a>
</div></li>
<li><strong>Design of SARS-CoV-2 protease inhibitors with improved affinity and reduced sensitivity to mutations</strong> -
<div>
Inhibitors of the SARS-CoV-2 main protease (Mpro) such as nirmatrelvir (NTV) and ensitrelvir (ETV) have proven effective in reducing the severity of COVID-19, but the presence of resistance-conferring mutations in sequenced viral genomes raises concerns about future drug resistance. Second-generation oral drugs that retain function on these mutants are thus urgently needed. We hypothesized that the covalent HCV protease inhibitor boceprevir (BPV) could serve as the basis for orally bioavailable drugs that inhibit SARS-CoV-2 Mpro more tightly than existing drugs. Performing structure-guided modifications of BPV, we developed a picomolar-affinity inhibitor, ML2006a4, with antiviral activity, oral pharmacokinetics, and therapeutic efficacy similar or superior to NTV. A crucial feature of ML2006a4 is a novel derivatization of the ketoamide reactive group that improves cell permeability and oral bioavailability. Finally, ML2006a4 is less sensitive to several mutations that cause resistance to NTV or ETV and occur in the natural SARS-CoV-2 population. Thus, anticipatory drug design can preemptively address potential resistance mechanisms.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.19.549739v1" target="_blank">Design of SARS-CoV-2 protease inhibitors with improved affinity and reduced sensitivity to mutations</a>
</div></li>
<li><strong>Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting</strong> -
<div>
The continuous emergence of highly immune evasive SARS-CoV-2 variants, like XBB.1.5 and XBB.1.16, highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by wildtype (WT)-based vaccination would compromise the antibody response to Omicron-based boosters. Vaccination strategies that can counter immune imprinting are critically needed. In this study, we investigated the degree and dynamics of immune imprinting in mouse models and human cohorts, especially focusing on the role of repeated Omicron stimulation. Our results show that in mice, the efficacy of single Omicron-boosting is heavily limited by immune imprinting, especially when using variants antigenically distinct from WT, like XBB, while the concerning situation could be largely mitigated by a second Omicron booster. Similarly, in humans, we found that repeated Omicron infections could also alleviate WT-vaccination-induced immune imprinting and generate high neutralizing titers against XBB.1.5 and XBB.1.16 in both plasma and nasal mucosa. By isolating 781 RBD-targeting mAbs from repeated Omicron infection cohorts, we revealed that double Omicron exposure alleviates immune imprinting by generating a large proportion of highly matured and potent Omicron-specific antibodies. Importantly, epitope characterization using deep mutational scanning (DMS) showed that these Omicron-specific antibodies target distinct RBD epitopes compared to WT-induced antibodies, and the bias towards non-neutralizing epitopes observed in single Omicron exposures due to imprinting was largely restored after repeated Omicron stimulation, together leading to a substantial neutralizing epitope shift. Based on the DMS profiles, we identified evolution hotspots of XBB.1.5 RBD and demonstrated the combinations of these mutations could further boost XBB.1.5’s immune-evasion capability while maintaining high ACE2 binding affinity. Our findings suggest the WT component should be abandoned when updating COVID-19 vaccine antigen compositions to XBB lineages, and those who haven’t been exposed to Omicron yet should receive two updated vaccine boosters.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.01.538516v4" target="_blank">Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting</a>
</div></li>
<li><strong>Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease</strong> -
<div>
Nonstructural protein 5 (Nsp5) is the main protease of SARS-CoV-2 that cleaves viral polyproteins into individual polypeptides necessary for viral replication. Here, we show that Nsp5 binds and cleaves human tRNA methyltransferase 1 (TRMT1), a host enzyme required for a prevalent post-transcriptional modification in tRNAs. Human cells infected with SARS-CoV-2 exhibit a decrease in TRMT1 protein levels and TRMT1-catalyzed tRNA modifications, consistent with TRMT1 cleavage and inactivation by Nsp5. Nsp5 cleaves TRMT1 at a specific position that matches the consensus sequence of SARS-CoV-2 polyprotein cleavage sites, and a single mutation within the sequence inhibits Nsp5-dependent proteolysis of TRMT1. The TRMT1 cleavage fragments exhibit altered RNA binding activity and are unable to rescue tRNA modification in TRMT1-deficient human cells. Compared to wildtype human cells, TRMT1- deficient human cells infected with SARS-CoV-2 exhibit reduced levels of intracellular viral RNA. These findings provide evidence that Nsp5-dependent cleavage of TRMT1 and perturbation of tRNA modification patterns contribute to the cellular pathogenesis of SARS-CoV-2 infection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.10.527147v2" target="_blank">Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease</a>
</div></li>
<li><strong>Faith and Outgroup Dehumanization During COVID</strong> -
<div>
We explore how Christians and Buddhists, of different religiosity, react to death within the context of the Covid-19 pandemic. Previous research has found that the interaction between cultural level, individual level and situational level factors are necessary to consider for a more comprehensive grasp of a phenomenon. We look at how Religion x Religiosity x Threat of Covid interact and show different relationships between these variables and dehumanization. We find that at higher levels of disruption by Covid-19 on religious practice (but not lower levels), Christians high on extrinsic religiosity (but low on intrinsic religiosity) dehumanized religious outgroups the most, whereas Christians high on extrinsic and high on intrinsic religiosity dehumanized religious outgroups significantly less. At low levels of impact of Covid-19 on religious practice, only higher levels of extrinsic religiosity were related to higher levels of dehumanization. Buddhists, regardless of level of religiosity and impact of Covid-19 to religious practice, consistently showed a relatively low level of dehumanization against religious outgroups. Findings are triangulated through multiple sources of data and further elaborated through qualitative coding of open-ended responses. These enactment patterns contribute to the religion and terror management literature and offer insights for potentially developing inclusive understanding with outgroup members.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/8xuhw/" target="_blank">Faith and Outgroup Dehumanization During COVID</a>
</div></li>
<li><strong>Predicting the impact of COVID-19 non-pharmaceutical intervention on short- and medium-term dynamics of enterovirus D68 in the US</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Recent outbreaks of enterovirus D68 (EV-D68) infections, and their causal linkage with acute flaccid myelitis (AFM), continue to pose a serious public health concern. During 2020 and 2021, the dynamics of EV-D68 and other pathogens have been significantly perturbed by non-pharmaceutical interventions against COVID-19; this perturbation presents a powerful natural experiment for exploring the dynamics of these endemic infections. In this study, we analyzed publicly available data on EV-D68 infections, originally collected through the New Vaccine Surveillance Network, to predict their short- and long-term dynamics following the COVID-19 interventions. Although there are large uncertainties in our predictions, the likelihood of a large outbreak in 2023 appears to be low. Comprehensive surveillance data are needed to narrow uncertainties in future dynamics of EV-D68. The limited incidence of AFM cases in 2022, despite large EV-D68 outbreaks, poses further questions for the timing of the next AFM outbreaks.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.14.23292680v2" target="_blank">Predicting the impact of COVID-19 non-pharmaceutical intervention on short- and medium-term dynamics of enterovirus D68 in the US</a>
</div></li>
<li><strong>Application of Machine Learning in Prediction of COVID-19 Diagnosis for Indonesian Healthcare Workers</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The COVID-19 pandemic poses a heightened risk to health workers, especially in low-and middle-income countries such as Indonesia. Due to the limitations of implementing mass RT-PCR testing for health workers, high-performing and cost-effective methodologies must be developed to help identify COVID-19 positive health workers and protect the spearhead of the battle against the pandemic. This study aimed to investigate the application of machine learning classifiers to predict the risk of COVID-19 positivity (by RT-PCR) using data obtained from a survey specific to health workers. Machine learning tools can enhance COVID-19 screening capacity in high-risk populations such as health workers in environments where cost is a barrier to the accessibility of adequate testing and screening supplies. We built two sets of COVID-19 Likelihood Meter (CLM) models: one trained on data from a broad population of health workers in Jakarta and Semarang (full model) and tested on the same, and one trained on health workers from Jakarta only (Jakarta model) and tested on both the same and an independent population of Semarang health workers. The area under the receiver-operating-characteristic curve (AUC), average precision (AP), and the Brier score (BS) were used to assess model performance. Shapely additive explanations (SHAP) were used to analyse future importance. The final dataset for the study included 5,393 healthcare workers. For the full model, the random forest was selected as the algorithm choice. It achieved cross-validation of mean AUC of 0.832 ± 0.015, AP of 0.513 ± 0.039, and BS of 0.124 ± 0.005, and was high performing during testing with AUC and AP of 0.849 and 0.51, respectively. The random forest classifier also displayed the best and most robust performance for the Jakarta model, with AUC of 0.856 ± 0.015, AP of 0.434 ± 0.039, and BS of 0.08 ± 0.0003. The performance when testing on the Semarang healthcare workers was AUC of 0.745 and AP of 0.694. Meanwhile, the performance for Jakarta 2022 test set was an AUC of 0.761 and AP of 0.535. Our models yielded high predictive performance and can be used as an alternative COVID-19 methodology for healthcare workers in Indonesia, therefore helping in predicting an increased trend of transmission during the transition into endemic.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.10.15.21265021v3" target="_blank">Application of Machine Learning in Prediction of COVID-19 Diagnosis for Indonesian Healthcare Workers</a>
</div></li>
<li><strong>Complete Protection from SARS-CoV-2 Lung Infection in Mice Through Combined Intranasal Delivery of PIKfyve Kinase and TMPRSS2 Protease Inhibitors</strong> -
<div>
Emerging variants of concern of SARS-CoV-2 can significantly reduce the prophylactic and therapeutic efficacy of vaccines and neutralizing antibodies due to mutations in the viral genome. Targeting cell host factors required for infection provides a complementary strategy to overcome this problem since the host genome is less susceptible to variation during the life span of infection. The enzymatic activities of the endosomal PIKfyve phosphoinositide kinase and the serine protease TMPRSS2 are essential to meditate infection in two complementary viral entry pathways. Simultaneous inhibition in cultured cells of their enzymatic activities with the small molecule inhibitors apilimod dimesylate and nafamostat mesylate synergistically prevent viral entry and infection of native SARS-CoV-2 and vesicular stomatitis virus (VSV)-SARS-CoV-2 chimeras expressing the SARS-CoV-2 surface spike (S) protein and of variants of concern. We now report prophylactic prevention of lung infection in mice intranasally infected with SARS-CoV-2 beta by combined intranasal delivery of very low doses of apilimod dimesylate and nafamostat mesylate, in a formulation that is stable for over 3 months at room temperature. Administration of these drugs up to 6 hours post infection did not inhibit infection of the lungs but substantially reduced death of infected airway epithelial cells. The efficiency and simplicity of formulation of the drug combination suggests its suitability as prophylactic or therapeutic treatment against SARS-CoV-2 infection in households, point of care facilities, and under conditions where refrigeration would not be readily available.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.19.549731v1" target="_blank">Complete Protection from SARS-CoV-2 Lung Infection in Mice Through Combined Intranasal Delivery of PIKfyve Kinase and TMPRSS2 Protease Inhibitors</a>
</div></li>
<li><strong>No evidence for the association between COVID-19 and neuroinflammation: A diffusion basis spectrum imaging study.</strong> -
<div>
COVID continues to be a major international public health concern, the underlying mechanisms of which are not fully understood. Recent studies suggest that COVID may cause prolonged inflammation within the central nervous system. However, the evidence so far has been limited to few small-scale case studies. To address this, this study leveraged a longitudinal dataset from the UK Biobank that included neuroimaging data prior to and following COVID testing (analytic N=416 including n=224 COVID-positive cases) and applied a novel and non-invasive Diffusion Basis Spectrum Imaging (DBSI) technique to derive putative indices of neuroinflammation (i.e., restricted fraction; DBSI-RF) for gray matter structures and white matter tracts in the brain. We hypothesized that SARS-CoV-2 infection would be associated with elevated DBSI markers of putative neuroinflammation and conducted linear regression analyses with adjustment for age, sex, race, body mass index, smoking frequency, and data acquisition interval. After multiple testing correction using false discovery rate, we found no evidence that COVID is associated with variability in neuroinflammation. Several brain regions showed nominally significant differences in DBSI-RF between COVID cases and controls including psychopathology-related regions linked that are either part of (i.e., orbitofrontal cortex) or functionally connected to the olfactory network (e.g., amygdala, caudate). It remains possible that there are acute and transitory neuroinflammatory effects associated with COVID that were not observed in our study due to potential resolution of COVID prior to the scan. Future research is warranted to examine whether neuroinflammation is associated with SARS-CoV-2 infection in a time- and/or symptom-dependent manner.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.20.549891v1" target="_blank">No evidence for the association between COVID-19 and neuroinflammation: A diffusion basis spectrum imaging study.</a>
</div></li>
<li><strong>Structure, Dynamics and Free Energy Studies on the Effect of Spot Mutations on SARS-CoV-2 Spike Protein Binding with ACE2 Receptor</strong> -
<div>
The ongoing COVID-19 pandemic continues to infect people worldwide, and the virus continues to evolve in significant ways which can pose challenges to the efficiency of available vaccines and therapeutic drugs and cause future pandemic. Therefore, it is important to investigate the binding and interaction of ACE2 with different RBD variants. A comparative study using all-atom MD simulations was conducted on ACE2 binding with 8 different RBD variants, including N501Y, E484K, P479S, T478I, S477N, N439K, K417N and N501Y-E484K-K417N on RBD. Based on the RMSD, RMSF, and DSSP results, the overall the binding of RBD variants with ACE2 is stable, and the secondary structure of RBD and ACE2 are consistent after the spot mutation. Besides that, a similar buried surface area, a consistent binding interface and a similar amount of hydrogen bonds formed between RBD with ACE2 although the exact residue pairs on the binding interface were modified. The change of binding free energy from spot mutation was predicted using the free energy perturbation (FEP) method. It is found that N501Y, N439K, and K417N can strengthen the binding of RBD with ACE2, while E484K and P479S weaken the binding, and S477N and T478I have negligible effect on the binding. Spot mutations modified the dynamic correlation of residues in RBD based on the dihedral angle covariance matrix calculation. Doing dynamic network analysis, a common intrinsic network community extending from the tail of RBD to central, then to the binding interface region was found, which could communicate the dynamics in the binding interface region to the tail thus to the other sections of S protein. The result can supply unique methodology and molecular insight on studying the molecular structure and dynamics of possible future pandemics and design novel drugs.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.19.549772v1" target="_blank">Structure, Dynamics and Free Energy Studies on the Effect of Spot Mutations on SARS-CoV-2 Spike Protein Binding with ACE2 Receptor</a>
</div></li>
<li><strong>Activated interstitial macrophages are a predominant target of viral takeover and focus of inflammation in COVID-19 initiation in human lung</strong> -
<div>
Early stages of deadly respiratory diseases such as COVID-19 have been challenging to elucidate due to lack of an experimental system that recapitulates the cellular and structural complexity of the human lung while allowing precise control over disease initiation and systematic interrogation of molecular events at cellular resolution. Here we show healthy human lung slices cultured ex vivo can be productively infected with SARS-CoV-2, and the cellular tropism of the virus and its distinct and dynamic effects on host cell gene expression can be determined by single cell RNA sequencing and reconstruction of “infection pseudotime” for individual lung cell types. This revealed that the prominent SARS-CoV-2 target is a population of activated interstitial macrophages (IMs), which as infection proceeds accumulate thousands of viral RNA molecules per cell, comprising up to 60% of the cellular transcriptome and including canonical and novel subgenomic RNAs. During viral takeover of IMs, there is cell-autonomous induction of a pro-fibrotic program (TGFB1, SPP1), and an inflammatory program characterized by the early interferon response, chemokines (CCL2, 7, 8, 13, CXCL10) and cytokines (IL6, IL10), along with destruction of cellular architecture and formation of dense viral genomic RNA bodies revealed by super-resolution microscopy. In contrast, alveolar macrophages (AMs) showed neither viral takeover nor induction of a substantial inflammatory response, although both purified AMs and IMs supported production of infectious virions. Spike-dependent viral entry into AMs was neutralized by blockade of ACE2 or Sialoadhesin/CD169, whereas IM entry was neutralized only by DC-SIGN/CD209 blockade. These results provide a molecular characterization of the initiation of COVID-19 in human lung tissue, identify activated IMs as a prominent site of viral takeover and focus of inflammation and fibrosis, and suggest therapeutic targeting of the DC-SIGN/CD209 entry mechanism to prevent IM infection, destruction and early pathology in COVID-19 pneumonia. Our approach can be generalized to define the initiation program and evaluate therapeutics for any human lung infection at cellular resolution.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.10.491266v2" target="_blank">Activated interstitial macrophages are a predominant target of viral takeover and focus of inflammation in COVID-19 initiation in human lung</a>
</div></li>
</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Smell in COVID-19 and Efficacy of Nasal Theophylline (SCENT 3)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: theophylline;   Drug: Placebo<br/><b>Sponsor</b>:   Washington University School of Medicine<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Lymph Node Aspiration to Decipher the Immune Response of Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine.</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Procedure: Lymph node aspiration / Blood sampling<br/><b>Sponsor</b>:   Assistance Publique - Hôpitaux de Paris<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Trial of the Candidate Vaccine MVA-SARS-2-S in Adults</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Biological: MVA-SARS-2-S;   Other: Placebo<br/><b>Sponsors</b>:   Universitätsklinikum Hamburg-Eppendorf;   German Center for Infection Research;   Philipps University Marburg Medical Center;   Ludwig-Maximilians - University of Munich;   University Hospital Tuebingen;   CTC-NORTH<br/><b>Withdrawn</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficiency and Safety of Paxlovid for COVID-19 Patients With Severe Chronic Kidney Disease</strong> - <b>Conditions</b>:   COVID-19;   Renal Insufficiency, Chronic<br/><b>Intervention</b>:   Drug: Nirmatrelvir/ritonavir<br/><b>Sponsor</b>:   Chinese PLA General Hospital<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Treatment of Long COVID (TLC) Feasibility Trial</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Low-dose Naltrexone (LDN);   Drug: Cetirizine;   Drug: Famotidine;   Drug: LDN Placebo;   Drug: Cetirizine Placebo;   Drug: Famotidine Placebo<br/><b>Sponsors</b>:   Emory University;   CURE Drug Repurposing Collaboratory (CDRC)<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety, Efficacy, and Dosing of VIX001 in Patients With Neurological Symptoms of Post Acute COVID-19 Syndrome (PACS).</strong> - <b>Conditions</b>:   Post-Acute COVID-19 Syndrome;   Cognitive Impairment;   Neurological Complication<br/><b>Intervention</b>:   Drug: VIX001<br/><b>Sponsor</b>:   Neobiosis, LLC<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PROTECT-APT 1: Early Treatment and Post-Exposure Prophylaxis of COVID-19</strong> - <b>Condition</b>:   SARS-CoV-2<br/><b>Interventions</b>:   Drug: Upamostat;   Drug: Placebo (PO)<br/><b>Sponsors</b>:   Henry M. Jackson Foundation for the Advancement of Military Medicine;   Joint Program Executive Office Chemical, Biological, Radiological, and Nuclear Defense Enabling Biotechnologies;   FHI Clinical, Inc.;   RedHill Biopharma Limited<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Efficacy, Safety, Tolerability and PK of SNS812 in Mild to Moderate COVID-19 Patients</strong> - <b>Condition</b>:   Disease Caused by Severe Acute Respiratory Syndrome Coronavirus 2 (Disorder)<br/><b>Interventions</b>:   Drug: MBS-COV;   Drug: Placebo<br/><b>Sponsor</b>:   Oneness Biotech Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Clinical Evaluation of the Safety and Efficacy of Randomized Placebo Versus the 8-aminoquinoline Tafenoquine for Early Symptom Resolution in Patients With Mild to Moderate COVID 19 Disease and Low Risk of Disease Progression</strong> - <b>Conditions</b>:   COVID 19 Disease;   Mild to Moderate COVID 19 Disease;   SARS-CoV-2;   Infectious Disease;   Severe Acute Respiratory Syndrome Coronavirus 2<br/><b>Interventions</b>:   Drug: Tafenoquine Oral Tablet;   Drug: Placebo<br/><b>Sponsor</b>:   60P Australia Pty Ltd<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of the Therapy With BRAINMAX® Using fMRI for the Treatment of Patients With Asthenia After COVID-19</strong> - <b>Conditions</b>:   Asthenia;   COVID-19;   Functional MRI;   Cognitive Impairment<br/><b>Interventions</b>:   Other: Structural and functional MRI;   Drug: Ethyl methyl hydroxypyridine succinate + Meldonium;   Drug: Placebo<br/><b>Sponsor</b>:   Promomed, LLC<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>NDV-HXP-S Vaccine Clinical Trial (COVIVAC)</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: COVIVAC vaccine<br/><b>Sponsors</b>:   Institute of Vaccines and Medical Biologicals, Vietnam;   National Institute of Hygiene and Epidemiology (NIHE), Vietnam;   Center for Disease Control of Thai Binh Province, Vietnam<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunoadsorption vs. Sham Treatment in Post COVID Patients With Chronic Fatigue Syndrome</strong> - <b>Conditions</b>:   Fatigue;   Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>:   Procedure: Immunoadsorption vs. sham immunoadsorption<br/><b>Sponsor</b>:   Hannover Medical School<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>MR-spectroscopy in Post-covid Condition Prior to and Following a Yoga Breathing Intervention</strong> - <b>Conditions</b>:   Post COVID-19 Condition;   Somatic Symptom Disorder<br/><b>Interventions</b>:   Behavioral: yoga;   Behavioral: social contact<br/><b>Sponsor</b>:   Medical University Innsbruck<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Evaluation of SARS-COV-2 (COVID-19), Influenza and RSV 8-Well MT-PCR Panel for In Vitro Diagnostics</strong> - <b>Condition</b>:   Respiratory Viral Infection<br/><b>Interventions</b>:   Diagnostic Test: SARS-COV-2, Influenza and RSV 8-Well MT-PCR Panel;   Diagnostic Test: BioFire Respiratory Panel 2.1<br/><b>Sponsor</b>:   AusDiagnostics Pty Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Expressive Interviewing Agents to Support Health-Related Behavior Change</strong> - <b>Condition</b>:   Mental Stress<br/><b>Intervention</b>:   Other: Expressive Interviewing<br/><b>Sponsors</b>:   University of Michigan;   University of Texas at Austin<br/><b>Completed</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Natural fucoidans inhibit coronaviruses by targeting viral spike protein and host cell furin</strong> - Fucoidans are a class of long chain sulfated polysaccharides and have multiple biological functions. Herein, four natural fucoidans extracted from Fucus vesiculosus, F. serratus, Laminaria japonica and Undaria pinnatifida, were tested for their HCoV-OC43 inhibition and found to demonstrate EC(50) values ranging from 0.15 to 0.61 µg/mL. That from U. pinnatifida exhibited the most potent anti-HCoV-OC43 activity with an EC(50) value of 0.15 ± 0.02 µg/mL, a potency largely independent of its sulfate…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>One master and two servants: One Zr(Ⅳ) with two ligands of TCPP and NH<sub>2</sub>-BDC form the MOF as the electrochemiluminescence emitter for the biosensing application</strong> - Here we put forward an innovative “one master and two servants” strategy for enhancing the ECL performance. A novel ECL luminophore named Zr-TCPP/NH(2)-BDC (TCPP@UiO-66-NH(2)) was synthesized by self-assembly of meso-tetra(4-carboxyphenyl)porphine (TCPP) and 4-aminobenzoic acid (NH(2)-BDC) with Zr clusters. TCPP@UiO-66-NH(2) has a porous structure and a highly ordered structure, which allows the molecular motion of TCPP to be effectively confined, thereby inhibiting nonradiative energy transfer….</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Understanding structure activity relationships of Good HEPES lipids for lipid nanoparticle mRNA vaccine applications</strong> - Lipid nanoparticles (LNPs) have shown great promise as delivery vehicles to transport messenger ribonucleic acid (mRNA) into cells and act as vaccines for infectious diseases including COVID-19 and influenza. The ionizable lipid incorporated within the LNP is known to be one of the main driving factors for potency and tolerability. Herein, we describe a novel family of ionizable lipids synthesized with a piperazine core derived from the HEPES Good buffer. These ionizable lipids have unique…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification and validation of fusidic acid and flufenamic acid as inhibitors of SARS-CoV-2 replication using DrugSolver CavitomiX</strong> - In this work, we present DrugSolver CavitomiX, a novel computational pipeline for drug repurposing and identifying ligands and inhibitors of target enzymes. The pipeline is based on cavity point clouds representing physico-chemical properties of the cavity induced solely by the protein. To test the pipeline’s ability to identify inhibitors, we chose enzymes essential for SARS-CoV-2 replication as a test system. The active-site cavities of the viral enzymes main protease (M^(pro)) and papain-like…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antibody Fc-binding profiles and ACE2 affinity to SARS-CoV-2 RBD variants</strong> - Emerging SARS-CoV-2 variants, notably Omicron, continue to remain a formidable challenge to worldwide public health. The SARS-CoV-2 receptor-binding domain (RBD) is a hotspot for mutations, reflecting its critical role at the ACE2 interface during viral entry. Here, we comprehensively investigated the impact of RBD mutations, including 5 variants of concern (VOC) or interest-including Omicron (BA.2)-and 33 common point mutations, both on IgG recognition and ACE2-binding inhibition, as well as…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A quantum chemical study on the anti-SARS-CoV-2 activity of TMPRSS2 inhibitors</strong> - Nafamostat and camostat are known to inhibit the spike protein-mediated fusion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by forming a covalent bond with the human transmembrane serine protease 2 (TMPRSS2) enzyme. Previous experiments revealed that the TMPRSS2 inhibitory activity of nafamostat surpasses that of camostat, despite their structural similarities; however, the molecular mechanism of TMPRSS2 inhibition remains elusive. Herein, we report the energy profiles of the…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of Sulforaphane on SARS‑CoV‑2 infection and NF‑κB dependent expression of genes involved in the COVID‑19 ‘cytokine storm’</strong> - Since its spread at the beginning of 2020, the coronavirus disease 2019 (COVID‑19) pandemic represents one of the major health problems. Despite the approval, testing, and worldwide distribution of anti‑severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) vaccines, the development of specific antiviral agents targeting the SARS‑CoV‑2 life cycle with high efficiency, and/or interfering with the associated ‘cytokine storm’, is highly required. A recent study, conducted by the authors’…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>New Viral Diseases and New Possible Remedies by Means of the Pharmacology of the Renin-Angiotensin System</strong> - All strains of SARS-CoV-2, as well as previously described SARS-CoV and MERS-CoV, bind to ACE2, the cell membrane receptor of β-coronaviruses. Monocarboxypeptidase ACE2 activity stops upon viral entry into cells, leading to inadequate tissue production of angiotensin 1-7 (Ang1-7). Acute lung injury due to the human respiratory syncytial virus (hRSV) or avian influenza A H7N9 and H5N1 viruses is also characterized by significant downregulation of lung ACE2 and increased systemic levels of…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Development of nanozymes for promising alleviation of COVID-19-associated arthritis</strong> - The COVID-19 pandemic caused by SARS-CoV-2 has been identified as a culprit in the development of a variety of disorders, including arthritis. Although the emergence of arthritis following SARS-CoV-2 infection may not be immediately discernible, its underlying pathogenesis is likely to involve a complex interplay of infections, oxidative stress, immune responses, abnormal production of inflammatory factors, cellular destruction, etc. Fortunately, recent advancements in nanozymes with enzyme-like…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Toxic effects of aging mask microplastics on E. coli and dynamic changes in extracellular polymeric matter</strong> - Contamination of disposable medical masks has become a growing problem globally in the wake of Covid-19 due to their widespread use and improper disposal. Three different mask layers, namely the outer layer, the meltblown (MB) filler layer and the inner layers release three different types of microplastics, whose physical and chemical properties change after prolonged environmental weathering. In this study, physical and chemical changes of mask microplastics before and after aging were…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>New cyclic arylguanidine scaffolds as a platform for development of antimicrobial and antiviral agents</strong> - According to WHO, infectious diseases are still a significant threat to public health. The combine effects of antibiotic resistance, immunopressure, and mutations within the bacterial and viral genomes necessitates the search for new molecules exhibiting antimicrobial and antiviral activities. Such molecules often contain cyclic guanidine moiety. As part of this work, we investigated the selected antimicrobial and antiviral activity of compounds from the cyclic arylguanidine group. Molecules…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>C-2 Thiophenyl Tryptophan Trimers Inhibit Cellular Entry of SARS-CoV-2 through Interaction with the Viral Spike (S) Protein</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, by infecting cells via the interaction of its spike protein (S) with the primary cell receptor angiotensin-converting enzyme (ACE2). To search for inhibitors of this key step in viral infection, we screened an in-house library of multivalent tryptophan derivatives. Using VSV-S pseudoparticles, we identified compound 2 as a potent entry inhibitor lacking cellular toxicity. Chemical optimization of 2 rendered compounds…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Modulation of NRF2: biological dualism in cancer, targets and possible therapeutic applications</strong> - SIGNIFICANCE: The NRF2-KEAP1 system is a master regulator of redox homeostasis and cell adaptation to a variety of exogenous and endogenous stressors. Accumulating evidence from the last decade indicates that the impairment of the redox balance leads to oxidative stress (OS), a common alteration occurring in many human acute and chronic inflammatory diseases,, such as cancer, diabetes, neurodegeneration, and metabolic disorders, and aging.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of low-intensity pulsed ultrasound in the treatment of COVID-19 pneumonia</strong> - Purpose As a public health emergency of international concern, the coronavirus disease 2019 (COVID-19) still lacks specific antiviral drugs, and symptomatic treatment is currently the mainstay. The overactivated inflammatory response in COVID-19 patients is associated with a high risk of critical illness or even death. Low-intensity pulsed ultrasound (LIPUS) can mitigate inflammation and inhibit edema formation. We aimed to investigate the efficacy of LIPUS therapy for COVID-19 pneumonia….</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Research Progress of Immunomodulation on Anti-COVID-19 and the Effective Components from Traditional Chinese Medicine</strong> - SARS-CoV-2 has posed a threat to the health of people around the world because of its strong transmission and high virulence. Currently, there is no specific medicine for the treatment of COVID-19. However, for a wide variety of medicines used to treat COVID-19, traditional Chinese medicine (TCM) plays a major role. In this paper, the effective treatment of COVID-19 using TCM was consulted first, and several Chinese medicines that were frequently used apart from their huge role in treating it…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A New Lawsuit Alleges That Leonard Leo Called for the Arrest of a Pro-Choice Protester</strong> - The court filing claims that the Federalist Society leader, a champion of free speech, urged police to violate the First Amendment rights of a demonstrator near his Maine home. - <a href="https://www.newyorker.com/news/news-desk/a-new-lawsuit-alleges-that-leonard-leo-called-for-the-arrest-of-a-pro-choice-protester">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Puzzling, Increasingly Rightward Turn of Mario Vargas Llosa</strong> - The writer has shocked many by endorsing Latin America and Spain’s rising authoritarian movements. - <a href="https://www.newyorker.com/news/daily-comment/the-puzzling-increasingly-rightward-turn-of-mario-vargas-llosa">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Day in the Life of Congress’s “Traffic Cop”</strong> - The House Committee on Rules decides which bills go forward. Jim McGovern, the ranking Democrat, has watched a decades-long erosion of the process. - <a href="https://www.newyorker.com/news/the-political-scene/a-day-in-the-life-of-jim-mcgovern-us-congress">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Is This the End of Bibi?</strong> - Netanyahu’s coalition of zealots, the resistance in the streets, and the Israeli Kulturkampf. - <a href="https://www.newyorker.com/news/daily-comment/is-this-the-end-of-benjamin-netanyahu">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Wrestling with the Ghost of Boris Johnson</strong> - An election for the seat in Parliament once held by the disgraced former Prime Minister goes down to the wire. - <a href="https://www.newyorker.com/news/letter-from-the-uk/wrestling-with-the-ghost-of-boris-johnson">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Why are fictional presidents so young?</strong> -
<figure>
<img alt="Actor Justin Kirk, as presidential candidate Jeryd Mencken, wears a black suit and attends a church service, with people seated in pews shown behind him." src="https://cdn.vox-cdn.com/thumbor/913w2duLdgV3LKcYlYXGLhrKo6w=/132x0:1839x1280/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72475920/justin_kirk.0.jpg"/>
<figcaption>
Justin Kirk as Jeryd Mencken on <em>Succession.</em> | Warner Bros.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Onscreen presidents tend to be youthful and dashing. Real presidents, less so.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="56hNWF">
<em>Welcome to </em><a href="https://www.vox.com/2019/2/1/18205669/design-culture-fashion-home-shopping-trends-movies-tv"><em><strong>Noticed</strong></em></a><em>, Vox’s cultural trend column. You know that thing you’ve been seeing all over the place? Allow us to explain it.</em>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SGPBpg">
<strong>What it is: </strong>They’re charming, fit, and usually good-looking, with Arlington-cemetery smiles and oilfield hair. There’s a decent chance they’ll have served in a familiar conflict like Iraq or Afghanistan. They can be found on either side of the political divide. A few of them are even women. They represent a new kind of politics, but you can’t vote for them because they only exist on our screens. They’re fictional presidents, and they’re young. So unbelievably young.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fJTst9">
<strong>Where it is: </strong>Across our screens, from <em>The Night Agent </em>to<em> Homeland</em>, but<em> </em>most recently, the final few episodes of <a href="https://www.vox.com/2019/9/29/20828679/succession-hbo-guide-season-four-episode-recaps-news-finale-waystar-royco"><em>Succession</em></a>. The Roy siblings worked out their familial kinks against the backdrop of an election, contested by new-broom Democrat Daniel Jiménez and flashy Republican Jeryd Mencken. Jiménez and Mencken were played by actors Elliot Villar, 43, and Justin Kirk, 54. Looking further back, shows like <em>Scandal</em>, <em>House of Cards </em>and multiple seasons of <em>24 </em>have all cast actors younger than 50 to play presidents or candidates. Fifty might well seem on the older side to you — the minimum age for a presidential candidate is a mere 35 — but in reality, the last time an election was contested by two people younger than half a century was 1960. In 2020, the combined age of both candidates was 151.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CEuMex">
<strong>Why you’re seeing it everywhere: </strong>One of the best lines from Oliver Stone’s 1995 biopic <em>Nixon</em> speaks to this phenomenon. In the depths of affliction, Richard Nixon — played by Anthony Hopkins with a grin so tight-lipped his mouth could be a fistula — addresses a portrait of JFK hanging in the White House. “When they look at you, they see what they want to be,” he says, staring up at the odd, pensive painting. “When they look at me, they see what they are.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mW66Zm">
As a summary of the difference between political rivals it works pretty well. Kennedy, an avatar of glamour and optimism, a youthful leader for a country that still believed its best years lay ahead. Nixon, a creature of sweat and resentment, the right man to lead a country that lost its way somewhere between the Bay of Pigs and Hanoi.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DfTECU">
The line also works pretty well as a summary of media aesthetics. For the most part, the entertainment industry doesn’t permit physical manifestations of the spiritual ugliness embodied by characters like Nixon (unless a real person is being dramatized, in which case handsome people will go to great lengths to give themselves a rough edge and an Oscar). Taking the improbably spelled Jeryd Mencken as an example, Kirk is fine-boned with a seductively fiendish energy, kind of like watching Gary Sinise through a bedeviling TikTok filter. He’s an election-stealing swine, but he looks the part. You can see why people would vote for him in droves.
</p>
<div class="c-float-right">
<aside id="9GXYZC">
<q>Only 10 percent of current senators are younger than 50</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SWDbZQ">
Of course, TV and film’s seldom-paid debt to reality is nothing new. Whether it’s what happens when a gas tank explodes or the attractiveness of patrons at a Philadelphia dive bar like Paddy’s Pub, the gap between world and screen is plenty wide. In recent years, the US has become a gerontocracy, with the last two presidential elections contested exclusively by candidates far older than normal retirement, and an upper house in which the <a href="https://www.pewresearch.org/short-reads/2023/01/30/house-gets-younger-senate-gets-older-a-look-at-the-age-and-generation-of-lawmakers-in-the-118th-congress/">average age of members is 65</a>. Only 10 percent of current senators are younger than 50. With Biden versus Trump in 2024 already looking like a grimly predictable bit of plotting, the age of its presidents might just represent the medium’s most absurdly unrealistic casting.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4ocpVa">
On screen we want our romantic leads flawless, our sitcom families lower middle-class but quirky, and our presidents capable of single-handedly killing terrorists and jumping out of crashing jumbo jets. Because running a country is hard and requires energy and patience — the kind that must be tough to come by when you’re painfully aware of the time you have left slipping away. More seriously, as Kennedy realized better than most, the president is an emblem as well as a politician. With the right leadership, maybe we could actually<em> </em>be what we want to be instead of settling for what we are.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CKLCNq">
Cinema and TV have no shame about pandering to us. But could their political preferences be more than just an aesthetic fantasy? Sure, it might be a little extreme to imagine the entire presidential line of succession being wiped out in a bombing so that Kiefer Sutherland can be sworn in on <em>Designated Survivor</em>. But while all the torture and extrajudicial executions from his <em>24 </em>days would certainly represent a lot of baggage, at least he didn’t oversee <a href="https://www.politico.com/news/magazine/2021/10/01/30-years-after-her-testimony-anita-hill-still-wants-something-from-joe-biden-514884">Clarence Thomas’s confirmation hearings</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1xj4K7">
One of storytelling’s most common functions is wish fulfillment, but sometimes it isn’t just the audience’s wishes that are being fulfilled. One of the frequent criticisms leveled at <em>The West Wing</em>, still perhaps the best-known and best-loved drama about a fictional presidency, was that it represented creator Aaron Sorkin’s personal fantasy of a principled, erudite politics, peopled by fast-talking characters who could say “I serve at the pleasure of the president” without exploding into balls of Miltonic rage. But while President Bartlet (played by Martin Sheen, 59 when the first season aired) is a Democrat’s dream, it is arguably the storyline about his successor that established the pattern.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4ICGjj">
In the later seasons after Sorkin’s departure, Bartlet’s presumed heir, Matt Santos, is the archetypal fantasy candidate. A former Marine, a family man, a Democrat from Texas. As played by a 49-year-old Jimmy Smits, he was also 6-foot-3 with a face chiseled from Mount Rushmore granite. His opponent, Arnold Vinick, was also a fantasy, but of a different sort: an avuncular Goldwater Republican played by the ever-affable Alan Alda. But he was spindly and silver-haired; unmistakably a politician of the past. (The actor was 68 at the time.) The writers gave themselves two candidates to root for, but it was clear that they only ever loved one of them.
</p>
<figure class="e-image">
<img alt="A blond man in a suit and tie under a navy coat." src="https://cdn.vox-cdn.com/thumbor/feEfaZS4yHSvt1jckt8sXpyxIQc=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24794806/HOC_413_00250r.JPG"/> <cite>Netflix</cite>
<figcaption>
Joel Kinnaman as Will Conway on <em>House of Cards.</em>
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aiwlVk">
And to prove the point that such make-believe can persist on either side of the aisle, <em>House of Cards </em>repeated the Santos playbook a decade later. Joel Kinnaman’s 37-year-old ubermensch Republican, Will Conway, took on the sleazy Underwoods just before Kevin Spacey’s disgraced exit from the show. Kinnaman spent two seasons projecting dignity while trying not to burst out of his tailoring. A presidential hopeful who could (and did) pass as a superhero. We should be so lucky.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="omxfYn">
Cormac McCarthy, who died in June, took the title of his novel <em>No Country for Old Men</em> from the poem “Sailing to Byzantium” by W.B. Yeats. In the poem, the elderly narrator laments that his homeland is now full of young people embracing, watching birds, and listening to sensual music. He doesn’t fit in, and decides to sail off in search of higher things. His destination is the city of Byzantium, where he hopes to transcend bodily frailty (possibly by asking some holy sages to eat his heart) and devote himself to “monuments of unageing intellect.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="D8ygsV">
This, of course, is the reason we’re often given for why we have to let a bunch of geriatrics make all the decisions. They have put behind them childish things, like the aforementioned music and embracing. They have the wisdom, the farsightedness, the unageing intellect needed to get the job done. Except that our lived experience shows that they don’t. What most of them really have are the barely submerged prejudices of their youth and an imperfect understanding of how <a href="https://www.vox.com/twitter">Twitter</a> works. We deserve better, and for once the unforgiving aesthetics of film and <a href="https://www.vox.com/tv">television</a> are pointing us to a truth we need to embrace.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ED3vk7">
After all, as Yeats’s poem goes on to remind us:
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YHAHaF">
“An aged man is but a paltry thing / A tattered (sport) coat upon a stick …”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3Tdhkk">
<em>Philip Walford lives in California and writes about technology and culture. You can find him on </em><a href="https://twitter.com/philipwalford"><em>Twitter</em></a><em>.</em>
</p></li>
<li><strong>No-kill chicken tastes like chicken. Because it is.</strong> -
<figure>
<img alt="Several meat skewers on a grill being brushed with sauce." src="https://cdn.vox-cdn.com/thumbor/ASkisFoDPoAhWTNUXUKGNAg5IFA=/0x120:958x839/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72475875/GOOD_Meat_at_China_Chilcano__June_2023____Photos_by_Ana_Isabel_Martinez_Chamorro_62_CROPPED__1_.0.jpg"/>
<figcaption>
Chicken grown directly from animal cells, also known as “cell-cultivated” meat, is prepared at José Andrés’s China Chilcano restaurant. | Eat Just
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Star chef José Andrés is piloting a lab-grown chicken dinner. Here’s what it tastes like.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SVsrS3">
I haven’t ordered meat at a restaurant in almost two decades, since I became a vegetarian in high school (and later, a vegan). But last week I found myself scarfing down two chicken skewers. My <a href="https://www.vox.com/future-perfect/2022/9/12/23339898/global-meat-production-forecast-factory-farming-animal-welfare-human-progress">ethical</a> and <a href="https://www.vox.com/future-perfect/23778399/media-ignores-climate-change-beef-meat-dairy">environmental</a> concerns around meat production hadn’t changed, but the chicken on my plate certainly had: It was grown directly from animal cells, with no live animal — and no animal slaughter — required.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MlMZqR">
The chicken in question was made by GOOD Meat — a division of the San Francisco Bay Area alternative protein startup <a href="https://www.ju.st/">Eat Just</a> — and the dinner marked a major milestone for the company: It was one of the very first times that so-called cell-cultivated meat had been served at a restaurant in the US.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yBpBdh">
Last month, after years of R&amp;D and hundreds of millions of dollars in VC funding, GOOD Meat and competitor Upside Foods <a href="https://www.vox.com/future-perfect/23768224/eat-just-good-meat-upside-cell-cultivated-chicken-lab-grown">received regulatory approval</a> to sell their slaughter-free chicken. (The meat is made by placing animal cells in large stainless steel tanks and feeding them sugars, amino acids, salts, vitamins, minerals, and other ingredients for several weeks until they develop into fat and muscle tissue.)
</p>
<div class="c-float-right">
<div id="s3GaVD">
<div>
</div>
</div>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="H1NIUy">
Despite the historic nature of the dinner, which was provided by Eat Just, there was little pomp and circumstance — just myself, a few fellow food and farming journalists, and two PR reps at a table in the middle of China Chilcano, a Peruvian-Chinese-Japanese fusion restaurant in Washington, DC, owned by chef and humanitarian José Andrés.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PoxMUJ">
The chicken, which was made up of 60 to 70 percent animal cells (the rest of it is plant-based — <a href="https://www.goodmeat.co/eat/cultivated-chicken">primarily wheat, soy, and oil</a>), had been marinated in an anticucho sauce and was served with potatoes and chimichurri.
</p>
<figure class="e-image">
<img alt="A close-up of two skewers of chicken and some potatoes." src="https://cdn.vox-cdn.com/thumbor/fD675rDOwJnCLVRfq5t07_tZkqs=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24799375/unnamed.jpg"/> <cite>Kenny Torrella/Vox</cite>
<figcaption>
Cell-cultivated chicken by Eat Just, served at chef José Andrés’s restaurant China Chilcano.
</figcaption>
</figure>
<h3 id="oOyqzS">
Close, but not quite chicken
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="01Fzxm">
To use the well-worn phrase, the slaughter-free chicken did taste like … chicken. It left behind a chickeny smell and a thin film of meaty oil in my mouth that I hadn’t experienced since I last ate meat, but was still familiar enough to be unmistakable. The anticucho sauce gave it a nice smoky flavor, and the exterior had a subtle crunch to it. I thought the texture could use some improvement — it seemed a little soft — but I haven’t had chicken in almost 20 years, so maybe I’m not the best judge.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qmLNgr">
If you want to give it a try yourself, the restaurant is <a href="https://www.chinachilcano.com/event/good-meat/">opening up reservations</a> on July 25, with service beginning on July 31. But it’ll be tough to get a spot. For one, the restaurant said it’s already received a flood of inquiries. But more importantly, it only has enough supply to serve eight guests a 3.5-ounce serving of cell-cultivated chicken per week, as part of an <a href="https://www.chinachilcano.com/menus/#good-chicken-tasting-menu-experience">extensive tasting menu</a> at $70 per person.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WNDyIy">
Bar Crenn, an upscale restaurant in San Francisco run by three-Michelin-star chef Dominique Crenn, opened up reservations on Thursday and will begin serving cell-cultivated chicken from Upside Foods on August 4. The six-course meal will cost $150 per person, with a 1-ounce serving of chicken made of 99 percent animal cells, and will only be <a href="https://www.sfchronicle.com/food/restaurants/article/cultivated-meat-bar-crenn-18201704.php">available</a> on the first weekend of each month with a capacity of 16 guests per month.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KeCi9w">
The stamp of approval from famed chefs like Crenn and Andrés should help startups get buy-in from the culinary world, and federal approval underscores that cell-cultivated meat is perfectly safe to eat. But the companies’ tiny supply and high prices — which still aren’t enough to prevent them from initially selling their chicken at a loss — highlight the immense challenges the whole sector faces in moving from a novelty food product to a commodity that can displace factory-farmed meat.
</p>
<h3 id="f2FS74">
Slaughter-free meat has come a long way — and has a longer way to go
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LWSptA">
When I first learned about cell-cultivated meat, George W. Bush was still in the White House, and there was no ecosystem of scientists, investors, and advocates cheerleading the technology as the future of food. There was just one tiny nonprofit dedicated to the issue, New Harvest, and there was the animal-rights group PETA, which offered a <a href="https://slate.com/technology/2008/04/why-peta-s-1-million-prize-for-artificial-meat-won-t-do-anything.html">$1 million prize</a> to anyone who could produce cell-cultivated meat at a price point comparable to conventional meat.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7PtU8n">
PETA’s stunt was clever, as it generated discussion around the need to innovate our way out of our meat-heavy food system and all the environmental, <a href="https://www.vox.com/animal-welfare">animal welfare</a>, and <a href="https://www.vox.com/public-health">public health</a> problems that stem from it. But the organization’s cash prize, and the high bar to win it, is now laughable. From 2016 to 2022, investors put <a href="https://gfi.org/wp-content/uploads/2023/01/2022-Cultivated-Meat-State-of-the-Industry-Report-2-1.pdf">nearly $3 billion</a> into over 150 cell-cultivated meat startups around the world — yet none are anywhere close to making it affordable.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YdvlU2">
The <a href="https://www.vox.com/the-highlight/23378912/meat-animals-beef-cultivated-in-vitro-food-plant-based-animal-welfare-impossible-burger">challenges</a> are both scientific and economic. Startups will need to figure out how to grow their cells faster, at higher densities, and with more affordable ingredients; ensure their large batches of meat are protected from bacterial contamination; and quickly build out massive and expensive production facilities.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="f220It">
To save on costs and scale up faster than their competitors, a handful of startups are making <a href="https://www.vox.com/the-highlight/23378912/meat-animals-beef-cultivated-in-vitro-food-plant-based-animal-welfare-impossible-burger">“hybrid” meats,</a> an emerging trend I reported on in detail late last year. Hybrid products are made primarily from plant-based ingredients, like a Beyond or Impossible burger, but with a small amount of animal cells to make them taste meatier. It’s a promising, incremental approach, but some in the sector argue that for the industry to reach its goal of displacing factory-farmed meat, it’ll need to make meat that is primarily made from animal cells. And funding from <a href="https://www.vox.com/venture-capital">venture capital</a> <a href="https://gfi.org/blog/fall-2022-reflections-from-gfi-founder-and-president-bruce-friedrich/">won’t suffice</a>; it’s going to need significant government money to get there.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4hvBOB">
The <a href="https://www.vox.com/energy">clean energy</a> analogy is often invoked in this space: Globally, direct investments, research grants, low-interest loans, and other spending from governments have been critical in scaling up renewable forms of energy and <a href="https://www.vox.com/electric-vehicles">electric vehicles</a>. Just since 2020, governments around the world have chipped in <a href="https://www.iea.org/news/global-government-spending-on-clean-energy-transitions-rises-to-usd-1-2-trillion-since-the-start-of-the-pandemic-spurred-by-energy-security-concerns">$1.2 trillion</a> through various means into clean energy development. By comparison, since 2020, governments have invested just <a href="https://public.tableau.com/app/profile/goodfood/viz/ExternalFundingDashboard1_0_16837527939270/ExternalFundingDashboard1_0">$1<em> </em>billion</a> into alternative protein sources (mostly <a href="https://www.vox.com/future-of-meat">plant-based meat</a>). Energy production deserves the larger support, given that it accounts for over <a href="https://www.epa.gov/ghgemissions/global-greenhouse-gas-emissions-data">one-third</a> of global greenhouse gas emissions, but conventional meat and dairy production is still responsible for around <a href="https://www.vox.com/future-perfect/23738600/un-fao-meat-dairy-livestock-emissions-methane-climate-change">15 percent</a> of global emissions.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Z91l6R">
The conversation around meat’s environmental footprint is far behind the conversation around <a href="https://www.vox.com/fossil-fuels">fossil fuels</a>, but that could change in the coming decades. The transition to clean energy is moving fast, but little is being done to curb agricultural emissions — so little that Boston Consulting Group <a href="https://www.ewg.org/news-insights/news/2023/02/will-agriculture-be-americas-leading-source-greenhouse-gas-emissions">estimates</a> that by 2050, if current trends continue, what Americans eat will be the country’s leading source of greenhouse gas emissions. Maybe, by then — more than 40 years after PETA’s cash prize offering — cell-cultivated meat will be on every restaurant menu. But it could be too late.
</p></li>
<li><strong>Thailand’s democracy could still move forward — even without Pita</strong> -
<figure>
<img alt="Move Forward Party Leader Pita Greets Supporters At The Beach" src="https://cdn.vox-cdn.com/thumbor/ovap0RbX2_xu7q9kfJq781VfIIQ=/407x0:6943x4902/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72475120/1562514225.0.jpg"/>
<figcaption>
Lauren DeCicca/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Thai politics could still change despite the best efforts of the military and the monarchy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CUIj3F">
Hopes for a progressive, democratic Thailand may be dashed after<strong> </strong>Pita Limjaroenrat and his Move Forward party were dealt a major blow Wednesday when the country’s parliament barred Pita from <a href="https://www.aljazeera.com/news/2023/7/19/protests-in-thailand-as-rivals-derail-pitas-pm-bid">standing a second time in elections for Prime Minister</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="W7U3D9">
The National Assembly also ousted Pita late Wednesday on recommendation of the Constitutional Court as it decides on the validity of his May candidacy in Thailand’s general elections. Pita had managed to build a multiparty parliamentary coalition, but failed to capture the necessary votes in an initial contest on July 13 though his party emerged as clear winners in Thailand’s general elections in May. Despite his coalition’s popularity — indicative particularly of young Thais’ frustration with a stalling <a href="https://www.vox.com/economy">economy</a> and massive inequality — their ideas for a more open society threaten Thailand’s entrenched monarchy and military leadership.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mF0oGG">
Now, a rare opportunity for major reform is at risk; though Thai people have demonstrated their support for Move Forward and Pita after their recent setbacks, attending rallies and organizing protests, the deeply entrenched power of the monarchy and the military may prove too overwhelming for progressive civilian governance to break through.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NMFVFr">
Thailand has a history of political turmoil, resulting in several military coups, including the most recent in 2014, which deposed democratically-elected Prime Minister <a href="https://www.britannica.com/biography/Yingluck-Shinawatra">Yingluck Shinawatra</a>. The present Prime Minister Prayuth Chan-ocha took power in 2014 and is a former army general, as well as the nation’s defense minister. Though Thailand has vacillated between a parliamentary democracy and military autocracy throughout the decades, it is technically a constitutional monarchy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="z1STzZ">
The monarchy is in one sense a treasured part of Thailand’s national character, part of a centuries-long tradition. But under the present king, <a href="https://www.economist.com/briefing/2020/10/14/thailands-king-seeks-to-bring-back-absolute-monarchy">Maha Vajiralongkorn</a>, Thailand’s government has experienced further democratic backsliding even as Thai people demand the opposite. Under Vajiralongkorn, the military and the monarchy make a powerful and often threatening combination; according to <a href="https://www.hrw.org/world-report/2022/country-chapters/thailand">Human Rights Watch</a>, the government arrested activists, suppressed pro-democracy protests, and instituted a nationwide state of emergency after massive and wide-ranging pro-democracy protests in 2020 and 2021. That protest movement was largely borne out of increasing government restrictions and demands to reform the monarchy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2tWdlj">
For both Thais and outside observers, Pita’s campaign and his coalition’s win in May presented a real possibility for change and growth in southeast Asia’s second largest economy. Now, given the government’s multivalent efforts to suppress the Move Forward coalition, an opportunity for real change is starting to look like a repeat of history — a seemingly ineluctable cycle of hope, unrest, and crackdowns edging further toward autocracy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RDSMU7">
“There’s a pattern here of establishment pushback against any progressive movement in Thai politics,” Thitinan Pongsudhirak, a political science professor at Chulalongkorn University told the <a href="https://www.nytimes.com/2023/07/13/world/asia/thailand-prime-minister-pita-limjaroenrat.htm">New York Times</a>. “And the pushback comes in different shapes and forms,”
</p>
<h3 id="Vt4os7">
Thailand’s constitutional monarchy is heavy on the monarchy
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WfDwpY">
Thailand has been a constitutional monarchy <a href="https://www.britannica.com/summary/Thailand">since 1932</a>, when a military coup abolished the absolute monarchy under <a href="https://www.britannica.com/biography/Prajadhipok">King Prajadhipok</a>. Despite that history, the Thai military establishment enjoys a close relationship with the monarchy — and they often work in concert to maintain a conservative and even autocratic government despite Thailand’s nominal embrace of democracy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nT1Xyr">
Prayuth and Vajiralongkorn have proven a formidable pair; during the 2020 and 2021 pro-democracy protests and calls to reform the monarchy, Prayuth’s government re-instituted punishment for <em>lèse-majèste</em>, or criticizing the monarchy. That policy, coupled with Covid-19 pandemic restrictions, enabled the government to detain and harshly punish thousands of pro-democracy protesters, according to <a href="https://www.hrw.org/world-report/2022/country-chapters/thailand#b7ff7e">Human Rights Watch</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="M7X9pp">
Under Prayuth, the military government has also consolidated power and made it even more difficult for ordinary Thai citizens to participate in government and actually have a choice regarding the future of their government, as <a href="https://www.vox.com/politics/2023/5/15/23724403/thailand-election-results-2023-pro-democracy-military-rule">Vox’s Li Zhou explained in May</a>:
</p>
<blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EFJdC6">
The military has long had a hold on Thai politics, a grip only strengthened by military coups in 2006 and 2014. That latter coup was led by current Prime Minister Prayuth Chan-ocha, who ushered in a new constitution that gave the military unprecedented power over government. One of those post-coup reforms threatens Move Forward’s coalition: 376 members of parliament are needed to elect a new prime minister, and the 250-person Senate was appointed by the military.
</p>
</blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gamyvp">
The military and monarchy hold significant sway over the political elite, including those who make up the Senate. That’s less pronounced in the democratically elected lower chamber, the House of Representatives, Brian Harding, senior expert on Southeast Asia and Pacific Islands at the US Institute for Peace told Vox in an interview. “If that were the only chamber, that in many ways reflects the will of the people,” he said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4FLd0H">
But the Senate has been “in lock step” with the government and the monarchy, Anthony Nelson, vice president in the East Asia and Pacific practice at Albright Stonebridge Group, told Vox.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="V72wGv">
“The constitution is basically functioning as intended; it’s protecting the monarchy, it’s allowing the conservative, establishment Thai parties to have a major, major veto over what happens.”
</p>
<h3 id="2mNAey">
Move Forward could still be pivotal to Thailand’s future
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="adKxY3">
The democratic movement in Thailand is about much more than Pita, although he has emerged as its charismatic face. His leadership in Move Forward is actually somewhat of an outgrowth of the pro-democracy protests, youth movements, and efforts on the part of Thai civil society.
</p>
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What is perhaps most salient about Pita is that he reflects the types of people who are drawn to Move Forward — young, well-educated, and progressive, people who ordinarily might be drawn to the traditional political elite, Nelson told Vox. That’s important for two reasons: It’s a departure from the country’s well-worn populist elected-to-military coup pipeline; and it’s an indicator that the newer generation is less socially stratified and more interested in building a forward-looking Thailand.
</p>
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Economically speaking, Thailand’s government is highly conservative; the country is a regional powerhouse but has never really broken out of its middle income status, and there has been relatively little encouragement for domestic innovation.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Db5qHo">
Thailand’s economy is highly globalized; it is a friendly place for foreign investment, has a robust <a href="https://www.vox.com/travel">tourism</a> industry, and is a part of the complex globalized supply chain. But there is a sense among Thai people, Nelson explained, that the fruits of the economy are largely concentrated at the very top.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FFqQ7L">
That’s not unfounded; in 2018 Thailand’s Crown Property Bureau <a href="https://www.ft.com/content/251d8aea-6939-4166-afe6-2df0176e0f8f">transferred about $40 billion</a> in assets including land titles and stakes in domestic corporations over to Vajiralongkorn to be “administered and managed at His Majesty’s discretion,” as the <a href="https://www.ft.com/content/251d8aea-6939-4166-afe6-2df0176e0f8f">Financial Times</a> reported in 2020. Thais protested the move, calling for more government transparency and reforming the monarchy, in some ways setting off the current pro-democracy movement.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="v1frlc">
Thailand also lacks a robust social safety net, though the government did implement <a href="https://blogs.worldbank.org/eastasiapacific/thai-economy-covid-19-poverty-and-social-protection#:~:text=These%20packages%20include%20soft%20loans,by%20the%20Social%20Security%20Fund">some social protection policies during the Covid-19 pandemic</a>, including cash payouts for workers in the informal sector and relaxed loan repayments.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eKsynD">
In addition to major political reforms like amending the <em>lèse-majèste </em>law and demanding more scrutiny of the defense apparatus, Move Forward offered a striking economic shift. The party proposed policies to build Thailand’s social safety net and raise wages “by raising taxes on corporations and on the wealthy, many of whom currently pay almost nothing in personal income tax,” Scott Christensen, an independent analyst, wrote in May for <a href="https://www.brookings.edu/articles/thailands-election-of-the-century/">the Brookings Institution</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="r3flfi">
Thailand has “found itself in a middle-income rut,” Nelson said, due to vested economic interests and monopolies in several industries including telecoms and alcohol sales. Move Forward had vowed to tackle those monopolies to foment innovation and competition — a position Thitinan told <a href="https://www.bloomberg.com/news/articles/2023-06-01/monopolies-dominating-thai-stocks-at-risk-after-election-shock">Bloomberg</a> would amount to “a complete transformation of the Thai economy.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FjpuSo">
At this point there is almost no possibility that Pita will be Thailand’s next leader; the country’s Constitutional Court is hearing a case alleging that he was unqualified to run in May’s election <a href="https://www.aljazeera.com/news/2023/7/19/thai-court-suspends-pita-as-mp-as-parliament-votes-on-new-premier">because he owns shares in a media company</a>, and the National Assembly has voted to prevent him from standing in the PM contest a second time.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eForcj">
However, Prayuth retired from politics July 11 following his party’s poor showing in the polls. Though he did not give a specific reason for his resignation, there is, potentially, at least some understanding that his government is deeply unpopular, as well as hope for a peaceful transition of power.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="S9aPdU">
Furthermore Pheu Thai, Move Forward’s populist coalition partner, <a href="https://asia.nikkei.com/Politics/Thai-election/Thailand-s-Move-Forward-yields-to-Pheu-Thai-candidate-for-PM#:~:text=Pheu%20Thai%20will%20announce%20on,former%20attorney%20general%20Chaikasem%20Nitisiri.">is set to field a candidate for a July 27 election</a>. Though Pheu Thai is more conservative and will likely have to work with populist military-backed parties in parliament, that could actually push the National Assembly in a more progressive direction, Nelson said. And if Pheu Thai wins the premiership, that would actually represent a significant shift from Thailand’s current politics.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="33V4ws">
“It was not all that long ago that there was a military coup to break Pheu Thai’s influence,” he said, referring to the 2007 coup that removed <a href="https://www.reuters.com/world/asia-pacific/thailands-ex-pm-thaksin-shakes-up-election-with-talk-return-2023-05-10/">Thaksin Shinawatra</a>, the party’s founder, from power. “So if what ends up happening from this is that they come back into power anyway — who knows to what degree they’ll be able to exercise it — but they’ll certainly be able to do something.”
</p>
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</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Deepak Ravikumar dominates first round of the MRF-MMSC-FMSCI National car racing championships</strong> - Ravikumar shuttled between the two categories barely without a pause to underline his supreme fitness and adaptability</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Satwik-Chirag win fourth title of year at Korea Open 2023</strong> - Satwik and Chirag extended their winning streak to 10 matches and added another feather to their cap, following their victory at the Swiss Open, Asian Championships and Indonesia Open this year.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Shubhankar Sharma stays in top-10 at Open</strong> - Sharma, who turned 27 on Friday, while moving into the tied-fourth place at the 151st Open, was still in the vicinity at 4-under through 36 holes. He was tied ninth, the third successive day he was in the top-10 of a Major.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Morning Digest | 18-year-old gang-raped in Manipur after women vigilantes hand her over to armed men; as tensions rise, Meiteis forced to leave Mizoram</strong> - Here is a select list of stories to start the day</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Carlos Alcaraz | A new heir to the tennis throne</strong> - 20-year-old Carlos Alcaraz reigning World No.1, who beat Djokovic in the Wimbledon final over five pulsating sets lasting nearly five hours, is bringing in a generational change in the sport</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-national-news">From The Hindu: National News</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Maharashtra landslide: NDRF calls off operation in Raigad; no body found on July 23, tolls stays at 27</strong> - So far, 27 bodies have been recovered while 57 are untraceable, officials said</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>India fast advancing on coastal research: Kiren Rijiju</strong> - PM Modi keen on expanding India’s role in ocean studies, says the Minister</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Three, including two students, die of electrocution in Palnadu, Bapatla districts</strong> - Two Intermediate students were killed when they came in contact with live wires while erecting banners to extend birthday wishes for a movie star</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Employees’ federation demands supply of quality food to Anganwadi centres in Andhra Pradesh</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Two killed in road accident in Eluru district</strong> -</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Spain faces stark left-right divide in hot summer vote</strong> - Resurgent nationalists in Spain aim to roll back the left-wing coalition’s reforms.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine war: Russian strikes on Odesa damage Orthodox cathedral</strong> - At least one person was killed and 19 injured in the blasts, including four children.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Rhodes fires: Jet2 and TUI flights cancelled as British tourists in limbo</strong> - Tourists left in limbo after wildfires spreading across the Greek island forced thousands to flee hotels.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Jamshid Sharmahd: Iran could execute my dad at any time, says German woman</strong> - An Iranian-German businessman on death row may have made his last phone call, his daughter fears.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Russian hardline Putin critic and commander Strelkov detained in Moscow</strong> - A key player in Russia’s Ukraine landgrab in 2014, he has bitterly criticised the flagging campaign.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-ars-technica">From Ars Technica</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Two great Star Trek shows revive the lost art of the gimmicky crossover episode</strong> - <em>Lower Decks</em> and <em>Strange New Worlds</em> have a lot of fun blending their styles. - <a href="https://arstechnica.com/?p=1955274">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Here’s the trailer for the live-action One Piece we’ve been waiting for</strong> - Netflix has a mixed track record when it comes to adapting beloved Japanese anime. - <a href="https://arstechnica.com/?p=1955937">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Long-forgotten frozen soil sample offers a warning for the future</strong> - Ancient soil was buried under a mile of ice until excavated during the Cold War. - <a href="https://arstechnica.com/?p=1955679">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Amazon is getting ready to launch a lot of broadband satellites</strong> - Amazon unveils satellite facility in Florida, may switch prototype launch to Atlas V - <a href="https://arstechnica.com/?p=1955951">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A promising Internet satellite is rendered useless by power supply issues</strong> - “The mission of providing Internet connectivity in Alaska will be delayed.” - <a href="https://arstechnica.com/?p=1955874">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A man badly damaged his dick in an accident</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The surgeon says “we’ve developed a new technique that can rebuild your penis, using a section of an elephant’s trunk”; so the guy decides to go ahead.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The operation is a great success. A couple of weeks later, he’s having dinner at a restaurant with his wife. Suddenly his dick bursts out of his pants, steals a bread roll and disappears with it under the table.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
His wife is absolutely astonished. “Do it again”, she says.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I would give it another go”, he replies, “but I don’t think my ass has room for another roll!”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/EditorRedditer"> /u/EditorRedditer </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/156tqsw/a_man_badly_damaged_his_dick_in_an_accident/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/156tqsw/a_man_badly_damaged_his_dick_in_an_accident/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>At a doll store</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Man: “Do you work here?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Lady: “Yes!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I need to buy a Barbie doll for my daughter. How much are they?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Which Barbie? We have Barbie goes to the gym for $19.95, Barbie goes to the ball for $19.95, Barbie goes to the beach for $19.95, Barbie goes shopping for $19.95, Barbie goes nightclubbing for $19.95, and divorced Barbie for $395.00.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Why is divorced Barbie so much more expensive than the others?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“It’s obvious! Divorced Barbie comes with Ken’s House, Ken’s car, Ken’s boat and Ken’s furniture”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/smooth_criminal_syd"> /u/smooth_criminal_syd </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1577nsx/at_a_doll_store/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1577nsx/at_a_doll_store/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What’s a nuclear engineer’s favourite meal?</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Fission chips!
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Different-Tie-1085"> /u/Different-Tie-1085 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/15794ob/whats_a_nuclear_engineers_favourite_meal/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/15794ob/whats_a_nuclear_engineers_favourite_meal/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>When a girl asks you “Does my butt looks big in this?” That is her way of asking you to set the difficulty for the evening…</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Easy mode: Of course not honey, you look wonderful.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Medium mode: Hmm, maybe try a different pair of pants.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Hard mode: Yes, but it looks big in anything.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Impossible mode: Yes, but on the bright side, it draws attention away from your face.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/lastson0fkrypton"> /u/lastson0fkrypton </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/156zb7w/when_a_girl_asks_you_does_my_butt_looks_big_in/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/156zb7w/when_a_girl_asks_you_does_my_butt_looks_big_in/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Be careful what you wish for…</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A man caught a goldfish and as always…
</p>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Let me go and I will grant you a wish”! - said the goldfish.
</p>
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“But I don’t need anything: I have a house, a summer house by the sea, cars, a cottage in the mountains, a yacht, more than enough money….. I only fish for pleasure” - he says.
</p>
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Come on, please, let me go, I’ll fulfill any wish”!!!
</p>
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Well, ok!”- says the guy “From now on I wish that my dear wife and I always have an orgasm together!” - and releases the fish!
</p>
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Voila, granted!” - says the little fish.
</p>
</li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The man picked up his fishing equipment, put it in the car and happily drove home….
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
On the way home he came twice!!!
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Gregib"> /u/Gregib </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/156hqju/be_careful_what_you_wish_for/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/156hqju/be_careful_what_you_wish_for/">[comments]</a></span></p></li>
</ul>
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